心肌灌注/代谢显像评价干细胞移植后犬受损心肌的修复能力

目的 采用核素心肌灌注(MPI)/代谢(MMI)显像评价犬心肌梗死自体骨髓干细胞移植后受损心肌的修复能力.方法 选取杂种犬12条,按动物编号法随机分为移植组(单号)及对照组(双号)各6条.通过手术间断阻断左前降支(LAD)下1/3循环90 min,建立犬心肌梗死模型.将诱导分化的骨髓间质干细胞自体移植到移植组动物梗死区,通过核素MPI和MMI、组织病理、免疫组织化学等技术评价干细胞移植治疗后6周和10周的效果.采用SPSS 10.0软件进行统计学处理.结果 (1)3条犬死亡,其中对照组2条.其余9条犬结扎冠状动脉24-48 h后的心电图、9～12 h后静脉血清心肌酶谱、5～7 d后MPI符合心肌梗死改变.(2)细胞移植后5～7 d MPI/MMI发现对照组心肌梗死节段数及梗死区存活心肌节段数分别为20及8个节段,移植组分别为25及10个节段,2组差异无统计学意义(t=0.389,P＞0.05).(3)ANOVA分析结果示,移植组有存活心肌的节段数在细胞移植10周与移植后5～7 d MPI/MMI比较差异有统计学意义(F=5.879,P＜0.05);无存活心肌的节段数细胞移植6周及10周MPI/MMI差异均无统计学意义(F=0.376,P＞0.05).对照组细胞移植后5～7 d、6周和10周的MPI/MMI所示梗死心肌节段数差异无统计学意义(F=0.212,0.005,0.316,P均＞0.05).(4)细胞移植5～7 d及10周后对照组与移植组的MPI所示左心室射血分数(LVEF)的变化值分别为(5.50±2.69)%及(16.20±2.93)%,2组之间差异有统计学意义(t=13.563,P＜0.01).结论 MPI/MMI不仅可以确定心肌梗死的部位、范围、程度及梗死心肌是否存活,还可以反映骨髓干细胞移植后的细胞存活及生长状况.

Assessment of the repair capability of infarcted myocardium in dogs after intracoronary delivery of mesenchymal stem cells using myocardial perfusion and metabolism imaging

Objective Bone marrow-derived mesenchymal stem cells(MSCs)can be used as a potential progenitor cell source for the regeneration of myocardium.The purpose of this study was to evaluate the repair capability of infarcted myocardium in dogs by myocardial perfusion and metabolism imaging(MPI/MMI)after intracoronary infusion of autologous MSCs.Methods Twelve dogs were randomly divided into two groups:6 in graft group and 6 in control group.Acute myocardial infarction(AMI)model was created by surgical blockade of myocardial blood flow in the distal 1/3 of left anterior descending artery(LAD)for 90 min.Then 0.9% NaCl and culture-expanded MSCs were grafted into the infarcted myocardium of the control and graft groups by intracoronary delivery.Electrocardiogram(ECG),serum biochemistry,MPI/MMI were performed in all subjects at 6 and 10 weeks after graft procedure.Pathological and immunohistochemical analysis was performed in all dogs at the end of the trial.SPSS 10.0 was used to analyse the data.Results Three dogs died during AMI modeling.The remaining 9 dogs that successfully passed AMI modcling were assessed by changes in ECG,serum creatine kinase(CK),CK-isoenzymes(MB),glutamate pyruvate transaminase(GPT),glutamic oxaloacetic transaminase(GOT)and MPI.The number of infarcted and viable myocardial segments,as evaluated by MPI/MMI 5-7 d after AMI,was 20 and 8 in the control group,and 25 and 10 in the graft group,respectively(t=0.389,P＞0.05,statistically insignificant).The difference between the number of viable myocardial segments at 5-7 d and at 10 weeks was statistically significant in the graft group(F=5.879,P＜0.05).But no changes in MPI/MMI were found among the 5-7 d,6 weeks and 10 weeks in control group(F=0.212,0.005,0.316;all P＞0.05)with ANOVA F test.The Ieft ventriculal ejection fraction(LVEF)changes between 5-7 d and 10 weeks in control and graft groups were(5.50±2.69)% and(16.20±2.93)%,respectively(t=13.563,P＜0.01).Conclusion Myocardial perfusion and metabolism imaging ale useful for assessment of changes in myocardial viability after stem cell transplantation.